1. Promoter hypermethylation of CDKN2A, MGMT, MLH1, and DAPK genes in laryngeal squamous cell carcinoma and their associations with clinical profiles of the patients
- Author
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Stefano, Pierini, Stanislav H, Jordanov, Atanaska V, Mitkova, Ivan J, Chalakov, Mincho B, Melnicharov, Kuncho V, Kunev, Vanio I, Mitev, Radka P, Kaneva, and Teodora E, Goranova
- Subjects
Adult ,Male ,Tumor Suppressor Proteins ,Nuclear Proteins ,DNA Methylation ,Middle Aged ,Death-Associated Protein Kinases ,DNA Repair Enzymes ,Carcinoma, Squamous Cell ,Prevalence ,Humans ,Female ,Bulgaria ,MutL Protein Homolog 1 ,Promoter Regions, Genetic ,DNA Modification Methylases ,Laryngeal Neoplasms ,Cyclin-Dependent Kinase Inhibitor p16 ,Adaptor Proteins, Signal Transducing ,Aged - Abstract
Laryngeal squamous cell carcinoma (laryngeal SCC) is a frequently occurring cancer of the head and neck area. Epigenetic changes of tumor-related genes contribute to its genesis and progression.We assessed promoter methylation status of the selected genes (CDKN2A, MGMT, MLH1, and DAPK) using methylation-sensitive high resolution melting (MS-HRM) in 100 patients with laryngeal SCC and studied the correlations with clinical characteristics.The prevalence of promoter methylation in MGMT, CDKN2A, MLH1, and DAPK was 59 of 97 (60.8%), 46 of 97 (47.4%), 45 of 97 (46.4%), and 41 of 97 patients (42.3%), respectively. Significantly increased methylation of CDKN2A was observed in heavy smokers. Epigenetic inactivation of CDKN2A and MLH1 were found to be associated with lymph node involvement. An inverse correlation was present between MLH1 methylation and alcohol consumption.Our results strongly suggest that deregulation of p16-associated, and MLH1-associated pathways, because of promoter hypermethylation, is associated with increased cancer cell migration, tumor invasiveness, and, thus, aggressive phenotype.
- Published
- 2012